Open Access. Powered by Scholars. Published by Universities.®

Medical Biochemistry Commons™

Open Access. Powered by Scholars. Published by Universities.®

School of Medicine Faculty Publications

Articles 1 - 26 of 26

Full-Text Articles in Medical Biochemistry

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari Aug 2025

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Go to article

Small Molecule Mcl-1 Inhibitor For Triple Negative Breast Cancer Therapy, Shengli Dong, Suresh K. Alahari Sep 2024

Small Molecule Mcl-1 Inhibitor For Triple Negative Breast Cancer Therapy, Shengli Dong, Suresh K. Alahari

School of Medicine Faculty Publications

Apoptosis is an evolutionarily conserved cell death pathway that plays a crucial role in maintaining tissue homeostasis, orchestrating organismal development, and eliminating damaged cells. Dysregulation of apoptosis can contribute to the pathogenesis of malignant tumors and neurodegenerative diseases. Anticancer drugs typically possess the capacity to induce apoptosis in tumor cells. The Bcl-2 protein family, consisting of 27 members in humans, serves as the key regulator of mitochondrial function. This family can be divided into two functional groups: anti-apoptotic proteins (e.g., Bcl-2, Bcl-xl, Mcl-1) and pro-apoptotic proteins (e.g., Bad, Bax). Mcl-1 exerts its function by binding pro-apoptotic Bcl-2 proteins thereby preventing …

Go to article

Characterizing The Monomer-Dimer Equilibrium Of Ubch8/Ube2l6: A Combined Saxs And Nmr Study, Kerem Kahraman, Scott A. Robson, Oktay Göcenler, Cansu M. Yenici, Cansu D. Tozkoparan Ceylan, Jennifer M. Klein, Volker Dötsch, Emine Sonay Elgin, Arthur L. Haas, Joshua J. Ziarek, Çağdaş Dağ Sep 2024

Characterizing The Monomer-Dimer Equilibrium Of Ubch8/Ube2l6: A Combined Saxs And Nmr Study, Kerem Kahraman, Scott A. Robson, Oktay Göcenler, Cansu M. Yenici, Cansu D. Tozkoparan Ceylan, Jennifer M. Klein, Volker Dötsch, Emine Sonay Elgin, Arthur L. Haas, Joshua J. Ziarek, Çağdaş Dağ

School of Medicine Faculty Publications

Interferon-stimulated gene-15 (ISG15) is an interferon-induced protein with two ubiquitin-like (Ubl) domains linked by a short peptide chain and is a conjugated protein of the ISGylation system. Similar to ubiquitin and other Ubls, ISG15 is ligated to its target proteins through a series of E1, E2, and E3 enzymes known as Uba7, Ube2L6/UbcH8, and HERC5, respectively. Ube2L6/UbcH8 plays a central role in ISGylation, underscoring it as an important drug target for boosting innate antiviral immunity. Depending on the type of conjugated protein and the ultimate target protein, E2 enzymes have been shown to function as monomers, dimers, or both. UbcH8 …

Go to article

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar May 2024

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …

Go to article

Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, Izhar Wallach, Denzil Bernard, Kong Nguyen, Gregory Ho, Adrian Morrison, Adrian Stecula, Andreana Rosnik, Ann Marie O’Sullivan, Aram Davtyan, Ben Samudio, Bill Thomas, Brad Worley, Brittany Butler, Christian Laggner, Desiree Thayer, Ehsan Moharreri, Greg Friedland, Ha Truong, Henry Van Den Bedem, Ho Leung Ng, Kate Stafford, Krishna Sarangapani, Kyle Giesler, Lien Ngo, Michael Mysinger, Mostafa Ahmed, Nicholas J. Anthis, Niel Henriksen, Arthur L. Haas, Et Al Apr 2024

Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, Izhar Wallach, Denzil Bernard, Kong Nguyen, Gregory Ho, Adrian Morrison, Adrian Stecula, Andreana Rosnik, Ann Marie O’Sullivan, Aram Davtyan, Ben Samudio, Bill Thomas, Brad Worley, Brittany Butler, Christian Laggner, Desiree Thayer, Ehsan Moharreri, Greg Friedland, Ha Truong, Henry Van Den Bedem, Ho Leung Ng, Kate Stafford, Krishna Sarangapani, Kyle Giesler, Lien Ngo, Michael Mysinger, Mostafa Ahmed, Nicholas J. Anthis, Niel Henriksen, Arthur L. Haas, Et Al

School of Medicine Faculty Publications

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, …

Go to article

Editorial: Reviews And Advances In The Molecular Mechanisms Of Breast Cancer, A. Redfern, V. Agarwal, Suresh Alahari Mar 2024

Editorial: Reviews And Advances In The Molecular Mechanisms Of Breast Cancer, A. Redfern, V. Agarwal, Suresh Alahari

School of Medicine Faculty Publications

No abstract provided.

Go to article

The Optimization Of A Natural Language Processing Approach For The Automatic Detection Of Alzheimer’S Disease Using Gpt Embeddings, Benjamin S. Runde, Ajit Alapati, Nicolas G. Bazan Feb 2024

The Optimization Of A Natural Language Processing Approach For The Automatic Detection Of Alzheimer’S Disease Using Gpt Embeddings, Benjamin S. Runde, Ajit Alapati, Nicolas G. Bazan

School of Medicine Faculty Publications

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel transcription methodologies. Specifically, we utilized Boll Spectral Subtraction to improve audio fidelity and created transcriptions using state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—evaluating their performance against traditional manual transcription methods. Support Vector Machine (SVM) classifiers were then trained and tested using GPT-based embeddings of transcriptions. Our findings revealed that AI-based transcriptions …

Go to article

Phenolic Acids Prevent Sex-Steroid Deficiency-Induced Bone Loss And Bone Marrow Adipogenesis In Mice, Perry C. Caviness, Oxana P. Lazarenko, Michael L. Blackburn, Jennifer F. Chen, Christopher E. Randolph, Jovanny Zabaleta, Fenghuang Zhan, Jin Ran Chen Feb 2024

Phenolic Acids Prevent Sex-Steroid Deficiency-Induced Bone Loss And Bone Marrow Adipogenesis In Mice, Perry C. Caviness, Oxana P. Lazarenko, Michael L. Blackburn, Jennifer F. Chen, Christopher E. Randolph, Jovanny Zabaleta, Fenghuang Zhan, Jin Ran Chen

School of Medicine Faculty Publications

Phenolic acids, such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA), can be produced from microbiome digestion of polyphenols. Previously it was found that HA and 3-3-PPA facilitate bone formation and suppress bone resorption. However, the mechanism of action by which HA and 3-3-PPA protect bone from degeneration is currently unknown. In this report, we present that HA and 3-3-PPA suppression of bone resorption is able to ameliorate bone loss in an ovariectomy (OVX) osteopenic mouse model though not to the extent of Zoledronic acid (ZA). HA and 3-3-PPA treatments were shown to significantly decrease bone marrow adipocyte-like cell …

Go to article

Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie Jan 2024

Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie

School of Medicine Faculty Publications

Background; Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. Methods; The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and …

Go to article

Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo Apr 2023

Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo

School of Medicine Faculty Publications

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a …

Go to article

Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow Apr 2023

Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow

School of Medicine Faculty Publications

The liver is a major organ that is involved in essential biological functions such as digestion, nutrient storage, and detoxification. Furthermore, it is one of the most metabolically active organs with active roles in regulating carbohydrate, protein, and lipid metabolism. Hepatocellular carcinoma is a cancer of the liver that is associated in settings of chronic inflammation such as viral hepatitis, repeated toxin exposure, and fatty liver disease. Furthermore, liver cancer is the most common cause of death associated with cirrhosis and is the 3rd leading cause of global cancer deaths. LKB1 signaling has been demonstrated to play a role in …

Go to article

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija Mar 2023

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija

School of Medicine Faculty Publications

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.

Go to article

Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert Mar 2023

Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert

School of Medicine Faculty Publications

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. …

Go to article

Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert Sep 2022

Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert

School of Medicine Faculty Publications

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of …

Go to article

An Rtn4/Nogo-A-Interacting Micropeptide Modulates Synaptic Plasticity With Age, S. Kragness, Z. Clark, A. Mullin, J. Guidry, L. R. Earls Jun 2022

An Rtn4/Nogo-A-Interacting Micropeptide Modulates Synaptic Plasticity With Age, S. Kragness, Z. Clark, A. Mullin, J. Guidry, L. R. Earls

School of Medicine Faculty Publications

Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity–Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Further, we find that Pants is secreted from neurons, where it …

Go to article

Nr4a Family Genes: A Review Of Comprehensive Prognostic And Gene Expression Profile Analysis In Breast Cancer, Hassan Yousefi, Jordyn Fong, Suresh K. Alahari Apr 2022

Nr4a Family Genes: A Review Of Comprehensive Prognostic And Gene Expression Profile Analysis In Breast Cancer, Hassan Yousefi, Jordyn Fong, Suresh K. Alahari

School of Medicine Faculty Publications

This report analyzes nuclear receptor (NR) subfamily 4A’s potential role in treating those diagnosed with breast cancer. Here we reviewed the current literature on NR4 family members. We also examined the relative gene expression of the NR4A receptor subfamily in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). These data showed a positive link between NR4A1-NR4A3 expression and increased overall survival and relapse-free survival in breast cancer patients. In addition, we observed …

Go to article

Evaluation Of Liver Kinase B1 Downstream Signaling Expression In Various Breast Cancers And Relapse Free Survival After Systemic Chemotherapy Treatment, Khoa Nguyen, Andrew Rivera, Madlin Alzoubi, Henri Wathieu, Shengli Dong, Hassan Yousefi, Margarite Matossian, Suresh Alahari, David Drewry, Matthew Burow, Bridgette Collins-Burow May 2021

Evaluation Of Liver Kinase B1 Downstream Signaling Expression In Various Breast Cancers And Relapse Free Survival After Systemic Chemotherapy Treatment, Khoa Nguyen, Andrew Rivera, Madlin Alzoubi, Henri Wathieu, Shengli Dong, Hassan Yousefi, Margarite Matossian, Suresh Alahari, David Drewry, Matthew Burow, Bridgette Collins-Burow

School of Medicine Faculty Publications

LKB1-signaling has prominent roles in cancer development and metastasis. This report evaluates LKB1-signaling pathway gene expression associations with patient survival in overall breast cancer, specific subtypes, as well as pre- and post-chemotherapy. Subtypes analyzed were based on intrinsic molecular subtyping and traditional biomarker classifications. Intrinsic molecular subtypes included were Luminal-A, Luminal-B, HER2-enriched, and Basal-like. The biomarker subtypes assessed were Estrogen-Receptor Positive (ER+) and Negative (ER-), Wild-Type TP53 (WT-TP53) & Mutant-TP53, and Triple-Negative Breast Cancer (TNBC). Additionally, comparisons were made between these subtypes and breast cancer overall, and analyses between LKB1 signaling to patient survival before and after chemotherapy were made. …

Go to article

Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan Oct 2020

Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan

School of Medicine Faculty Publications

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …

Go to article

Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi Oct 2020

Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi

School of Medicine Faculty Publications

The Unfolded Protein Response pathway is a conserved signaling mechanism having important roles in cellular physiology and is perturbed accompanying disease. We previously identified the novel UPR target gene CHAC1, a direct target of ATF4, downstream of PERK-EIF2A and activated by the UPR pathway. CHAC1 enzyme directs catalysis of γ-linked glutamate bonds within specific molecular targets. CHAC1 is the first enzyme characterized that can catalyze intracellular glutathione degradation in eukaryotes, having implications for regulation of oxidative stress. DDIT3 (CHOP) is a terminal UPR transcription factor, regulated by ATF4 and an output promoting cell death signaling. Herein we examine the relationship …

Go to article

Chemically Modified Variants Of Fenofibrate With Antiglioblastoma Potential, J Stalinska, E Zimolag, N. A. Pianovich, A Zapata, A Lassak, M Rak, M Dean, D Ucar-Bilyeu, D Wyczechowska, F Culicchia, L Marrero, Luis Del Valle, J Sarkaria, F Peruzzi, B. S. Jursic, K. Reiss May 2019

Chemically Modified Variants Of Fenofibrate With Antiglioblastoma Potential, J Stalinska, E Zimolag, N. A. Pianovich, A Zapata, A Lassak, M Rak, M Dean, D Ucar-Bilyeu, D Wyczechowska, F Culicchia, L Marrero, Luis Del Valle, J Sarkaria, F Peruzzi, B. S. Jursic, K. Reiss

School of Medicine Faculty Publications

Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffective effective in triggering cancer cell death. To address these issues, we have …

Go to article

Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio Jan 2018

Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio

School of Medicine Faculty Publications

Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic …

Go to article

A Mirna Signature For Cognitive Deficits And Alcohol Use Disorder In Persons Living With Hiv/Aids, Dorota Wyczechowska, Hui-Yi Lin, Andrea Laplante, Duane Jeansonne, Adam Lassak, Christopher H. Parsons, Patricia E. Molina, Francesca Peruzzi Nov 2017

A Mirna Signature For Cognitive Deficits And Alcohol Use Disorder In Persons Living With Hiv/Aids, Dorota Wyczechowska, Hui-Yi Lin, Andrea Laplante, Duane Jeansonne, Adam Lassak, Christopher H. Parsons, Patricia E. Molina, Francesca Peruzzi

School of Medicine Faculty Publications

HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have …

Go to article

Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi Nov 2015

Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi

School of Medicine Faculty Publications

The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …

Go to article

Anti-Tumoral Effects Of Mir-3189-3p In Glioblastoma, Duane Jeansonne, Mariacristina Deluca, Luis Marrero, Adam Lassak, Marco Pacifici, Dorota Wyczechowska, Anna Wilk, Krzysztof Reiss, Francesca Peruzzi Feb 2015

Anti-Tumoral Effects Of Mir-3189-3p In Glioblastoma, Duane Jeansonne, Mariacristina Deluca, Luis Marrero, Adam Lassak, Marco Pacifici, Dorota Wyczechowska, Anna Wilk, Krzysztof Reiss, Francesca Peruzzi

School of Medicine Faculty Publications

Glioblastoma is one of the most aggressive brain tumors. We have previously found up-regulation of growth differentiation factor 15 (GDF15) in glioblastoma cells treated with the anticancer agent fenofibrate. Sequence analysis of GDF15 revealed the presence of a microRNA, miR-3189, in the single intron. We then asked whether miR-3189 was expressed in clinical samples and whether it was functional in glioblastoma cells. We found that expression of miR-3189-3p was down-regulated in astrocytoma and glioblastoma clinical samples compared with control brain tissue. In vitro, the functionality of miR-3189-3p was tested by RNA-binding protein immunoprecipitation, and miR-3189-3p coimmunoprecipitated with Argonaute 2 together …

Go to article

Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai Nov 2014

Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai

School of Medicine Faculty Publications

MicroRNAs (miRNAs) are small non-coding RNA species that can bind to both untranslated and coding regions of target mRNAs, causing their degradation or post-transcriptional modification. Currently, over 2500 miRNAs have been identified in the human genome. Burgeoning evidence suggests that dysregulation of human miRNAs can play a role in the pathogenesis of a variety of diseases, including cancer. In contrast, only a small subset of human miRNAs has been functionally validated in the pathogenesis of oncogenic viruses, in particular, Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the etiologic agent of several human cancers, such as primary effusion lymphoma (PEL) and Kaposi's …

Go to article

Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi Mar 2013

Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi

School of Medicine Faculty Publications

Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an …

Go to article